Boisivon A, Guiomar C, Gutmann L
Service de Microbiologie, Hôpital de Saint Germain-en-Laye, France.
J Antimicrob Chemother. 1988 Nov;22(5):651-7. doi: 10.1093/jac/22.5.651.
Pseudomonas aeruginosa mutants were selected with piperacillin, pefloxacin, amikacin and the combinations pefloxacin-piperacillin and amikacin-piperacillin. With amikacin and the piperacillin-amikacin combination no mutants were selected. With piperacillin (1-32 x MIC) mutants resistant to carboxypenicillins, ureidopenicillins, monobactam and cephalosporins were selected. With pefloxacin, three different types of mutant were observed which showed different patterns of cross-resistance to pefloxacin, sulphonamides, imipenem, piperacillin and other beta-lactam antibiotics. With the pefloxacin-piperacillin association, mutants similar to one of the types selected by pefloxacin alone and resistant to both of the selective antibiotic were predominantly obtained. No mutants were selected with this combination if one of the antibiotics was used at a concentration equal to its MIC for the wild type strain and the other at concentrations above 4 x MIC. Since the association of piperacillin and pefloxacin was only moderately bactericidal against the predominantly cross-resistant mutant selected, the concentration of these antibiotics may have to be carefully controlled to prevent the emergence of such mutants.
用哌拉西林、培氟沙星、阿米卡星以及培氟沙星 - 哌拉西林和阿米卡星 - 哌拉西林组合筛选铜绿假单胞菌突变体。使用阿米卡星以及哌拉西林 - 阿米卡星组合未筛选到突变体。使用哌拉西林（1 - 32倍最低抑菌浓度）筛选到了对羧苄青霉素、脲基青霉素、单环β - 内酰胺类抗生素和头孢菌素耐药的突变体。使用培氟沙星时，观察到三种不同类型的突变体，它们对培氟沙星、磺胺类药物、亚胺培南、哌拉西林和其他β - 内酰胺类抗生素表现出不同的交叉耐药模式。使用培氟沙星 - 哌拉西林组合时，主要获得了与单独使用培氟沙星筛选出的一种类型相似且对两种选择性抗生素均耐药的突变体。如果其中一种抗生素以其对野生型菌株的最低抑菌浓度使用，另一种以高于4倍最低抑菌浓度使用，则用该组合未筛选到突变体。由于哌拉西林和培氟沙星组合对主要筛选出的交叉耐药突变体仅有中等杀菌作用，可能必须仔细控制这些抗生素的浓度以防止此类突变体的出现。
